We are investigating the molecular mechanism of action of the suppressor of sable [su(s)] system of Drosophila melanogaster. Recessive su(s) mutations suppress recessive second-site mutations that are caused by insertions of the mobile elements 412 and P in 5' transcribed but nontranslated sequences. Current evidence suggests that this suppression is effected by some mechanism that increases the amount of pseudo-wild-type mRNA that is produced by splicing the mobile element sequences from the primary transcript. The su(s) cDNA contains an open reading frame that encodes a putative polypeptide of 1322 amino acids, and cellular fractionation studies have shown that the protein is primarily located in the nucleus. This protein has only one region of general similarity to other proteins: a highly charged region that is similar to a putative nuclear localization signal found in several human, Xenopus and Drosophila proteins, all of which are known to be RNA binding proteins. Males and females lacking the entire su(s) protein are viable and fertile, albeit markedly below the levels of viability and fertility of wild-type flies. Because the su(s) protein has very limited similarity to other proteins, the important functional domains of the protein are being identified by determining which regions of the protein have been evolutionarily conserved. The su(s) gene of the distantly related Drosophila virilis has been cloned and partially sequenced, and it contains both regions of high homology and of considerable divergence. We are also attempting to clone the su(s) gene from the very distantly related flour beetle, Tribolium castaneum, for similar studies.